The purpose of this work is to clarify the nature of molecules responsible for converting a normal cell to its malignant form by studying the nature of temperature-sensitive (ts) or cold-sensitive (cs) mutants of Chinese hamster lung cells affected in the expression of the transformed state. Several ts- and cs-sensitive mutants were isolated and confirmed to show the normal phenotype at non-permissive temperature and the transformed phenotype at permissive temperature. The resistance to 6-thioguanine or ouabain was introduced into these mutants for further studies.